The rise of immuno-oncology is transforming cancer treatment, leveraging the body's immune system to combat the disease. In a recent interview, Dr. Alexander Ariel Padrón González, Director of Regulatory Affairs at SASMAR PHARMA, talked with Muhammad Younis about its standing among traditional therapies, key breakthroughs, and the metrics proving its effectiveness. He also addressed the challenges of cost and accessibility, exploring innovations to make these treatments more affordable. Looking ahead, the discussion touched on emerging therapies poised to revolutionise cancer care in the coming years.

 #LBS: Where does immuno-oncology currently stand among various traditional treatments for diverse cancer types? What key metrics validate its superiority?

Dr Alexander: Immuno-oncology's role in cancer treatment is evolving rapidly:

  • Combination Therapy Role: IO is increasingly used with traditional treatments to enhance efficacy. For example, immune checkpoint inhibitors (like PD-1/PD-L1 blockers) are often paired with chemotherapy or radiation to achieve better outcomes. Examples: 
    • Pembrolizumab + Carboplatin, pemetrexed (KEYNOTE-021). Advanced or metastatic NSCLC
    • Atezolizumab + Carboplatin, paclitaxel (IMpower150). Stage IV non-squamous NSCLC
    • Ipilimumab + Radiotherapy. Advanced melanoma Phase III
    • Chemotherapy + Radiotherapy + Durvalumab. Metastatic non-small cell lung cancer and Phase III     
  • Shift to First-Line Therapy: In several cancers, IO is now approved as a first-line therapy, especially for metastatic and advanced cancers (e.g., pembrolizumab for advanced nonsmall cell lung cancer (NSCLC) and melanoma).
  • Targeting Unmet Needs: IO shows remarkable results in cancers with poor prognosis or those resistant to traditional therapies, such as metastatic melanoma or triple-negative breast cancer (TNBC).
  • Expanding Scope: Beyond advanced cancers, IO is being explored in earlier-stage cancers (neoadjuvant and adjuvant settings), as well as in combination with targeted therapies (e.g., Vemurafenib + Ipilimumab in advanced or metastatic melanoma).

 Some of the key metrics highlighting IO’s superiority are:

  • Overall Survival (OS): IO therapies consistently demonstrate superior OS compared to traditional treatments. For instance:
    • NSCLC: In CheckMate 227 Part, first-line nivolumab plus ipilimumab prolonged overall survival (OS) in patients with metastatic non-small-cell lung cancer (NSCLC) and tumor programmed death-ligand 1 (PD-L1) expression ≥1% versus chemotherapy. 
    • Pembrolizumab Versus Chemotherapy as First-Line Therapy in Patients With Non–SmallCell Lung Cancer: First-line pembrolizumab monotherapy continued to show durable clinical benefit versus chemotherapy after 5 years of follow-up in PD-L1–positive in the KEYNOTE042 Study
  • Progression-Free Survival (PFS): Many IO treatments prolong the time patients live without disease progression- The phase 3 JAVELIN Renal 101 trial of avelumab + axitinib vs sunitinib in patients with treatment-naive advanced renal cell carcinoma (RCC) demonstrated significantly improved progression-free survival (PFS) and higher objective response rate (ORR) with the combination vs sunitinibDurable Responses:
  • Reduced Treatment Burden: Compared to chemotherapy, which often requires continuous cycles, IO can deliver results with fewer treatments, improving quality of life (QoL). For example, In some cases of early NSCLC, a single dose of neoadjuvant nivolumab induces significant pathological tumour regression.
  • Combination Therapy Synergy: IO enhances the effectiveness of traditional therapies as previously described

 #LBS: Could you share specific cases or breakthrough treatments that highlight the effectiveness of immuno-oncology in treating various cancer types, and what lessons these successes offer for tackling other cancers?

Dr Alexander:

  •  KEYNOTE-189 trial: In patients with previously untreated metastatic nonsquamous NSCLC without EGFR or ALK mutations, the addition of pembrolizumab to standard chemotherapy of pemetrexed and a platinum-based drug resulted in significantly longer overall survival and progression-free survival than chemotherapy alone.
  • Immune checkpoint inhibitors currently represent the most promising in clinical trials for NSCLC, RCC, kidney cancers, and melanoma, where even monotherapies can produce durable responses in 40-50% of patients, persisting long after treatment has ceased.
  • Adoptive T-cell therapy:  Many clinical trials are underway against melanoma, lymphoma and leukemias.  
  • Oncolytic viruses: T-VEC became FDA-approved in 2015 as Imlygic for patients with inoperable cancers. Other clinical trials are ongoing for pancreatic, breast and colorectal cancers.
  • Vaccines: FDA-approved vaccines include: Oncophage for kidney cancer, and sipuleucel-T for metastatic prostate cancer. Many are entering clinical development.

#LBS: Cost and accessibility remain significant challenges for immuno-oncology therapies. What strategies or innovations could make these treatments more affordable and widely available, particularly in low-resource settings?

Dr Alexander:  

  • Use of Biosimilars: Developing biosimilars (lower-cost, clinically equivalent versions of biologics) can drastically reduce costs.
  • Streamlined Bioprocessing Technologies: Advances like single-use bioreactors and continuous manufacturing can lower production costs by reducing waste and increasing efficiency. 
  • mRNA and DNA platforms: Emerging platforms like mRNA vaccines (e.g., personalized cancer vaccines) are less expensive to produce and distribute than monoclonal antibodies, given their scalability and synthetic manufacturing processes.
  • Localized production: Establishing regional biomanufacturing hubs in low- and middle-income countries (LMICs) reduces shipping costs, tariffs, and cold-chain logistics expenses.
  • Modular Facilities: Portable, modular biomanufacturing units can be deployed to produce small batches of IO therapies on-site, reducing dependence on centralized facilities.
  • Risk-Sharing agreements: Value-based pricing models, where payers only pay if the therapy works for a patient, are gaining traction.
  • Tiered Pricing: Pharmaceutical companies can adopt tiered pricing based on a country’s income level.
  • Expanded Access Programs: Governments and non-profits can facilitate expanded access programs that provide free or discounted drugs to underserved populations.
  • Shortened Treatment Regimens: Reducing the frequency or duration of IO therapy can significantly lower costs.
  • Oral and Subcutaneous Formulations: Transitioning from intravenous to subcutaneous or oral forms of IO therapies reduces hospital administration costs and increases patient convenience.
  • Precision Medicine Approaches: Improving patient selection through biomarker-driven strategies (e.g., PD-L1 expression, tumor mutation burden) ensures IO therapies are given to those most likely to benefit, reducing unnecessary treatments.
  • Artificial Intelligence (AI): AI can predict which patients are most likely to respond to therapy, improving resource allocation and reducing overall costs.

 #LBS: The field of immuno-oncology is evolving rapidly. What groundbreaking therapies are on the horizon, and how might they revolutionise cancer treatments in the coming years?

Dr Alexander: Currently, there are many groundbreaking therapies in immunotherapies on the horizon, making it difficult to address this topic in a simplified manner. From my personal perspective, some of the potential approaches are:

  • Personalized Cancer Vaccines & Breakthrough Therapies: mRNA Cancer Vaccines; Leveraging mRNA technology (similar to COVID-19 vaccines), to develop personalized cancer vaccines tailoring to individual tumor profiles and reducing off-target effects. Advances in mRNA technology allow rapid development, scalability, and production for diverse cancers.
  • Bispecific Antibodies (BsAbs) & Breakthrough Therapies:
    • Rybrevant approved in 2021 to treat locally advanced or metastatic non-small cell lung cancer with certain mutations.
    • Tecvayli approved in 2022 to treat relapsed or refractory multiple myeloma.
    • Epkinly approved in 2023 to treat relapsed or refractory diffuse large B-cell lymphoma.
    • Columvi approved in 2023 to treat relapsed or refractory diffuse large B-cell lymphoma or large B-cell lymphoma.

These BsAbs effective in "cold tumors" offering precision targeting with reduced toxicity compared to traditional IO therapies.

  • CAR Cell Therapy
    • Allogeneic (“Off-the-Shelf”) CAR-T Cells: Autologous chimeric antigen receptor (CAR) T cells have changed the therapeutic landscape in haematological malignancies.  The use of allogeneic CAR T cells from donors has many potential advantages over autologous approaches, such as the immediate availability of cryopreserved batches for patient treatment, possible standardization of the CAR-T cell product, time for multiple cell modifications, redosing or combination of CAR T cells directed against different targets, and decreased cost using an industrialized process. 
    • Dual-Targeting CAR-T Cells: dual-targeted chimeric antigen receptor (CAR) T-cell therapy has been employed in the management of hematological malignancies to mitigate treatment failure, particularly in cases of antigen escape. The most widely used approaches include CD19/CD20, CD20/CD22, and BCMA/CD19 CAR T-c Another interesting possibility is the development of CAR in other immune cells such as Natural Killer, gamma delta T cells, Neutrophils etc.
    • Tumor-Infiltrating Lymphocyte (TIL) Therapy - Lifileucel: The FDA approved Lifileucel (TIL therapy) in March 2024 for advanced melanoma. Iovance has already started enrolling participants in a large trial combining lifileucel with the immunotherapy drug pembrolizumab (Keytruda) as an initial treatment for advanced melanoma. Lifileucel is also well along in testing as a treatment for other cancers, including showing promising tumor responses in people with advanced lung cancer, as well as ovarian and head and neck cancers. TIL therapy offers high efficacy in immune-resistant tumors and personalized and tailored to individual patients’ immune responses.
    • Immune Agonists (Next-Gen Checkpoint Modulators): PD-(L)1, CTLA-4 and LAG-3 are the only immune-checkpoints with proven efficacy. However primary and acquired resistance can involve upregulation of immunecheckpoints. For that reason promising novel targets include ICOS, VISTA, TIGIT, CD112R, BTLA, TIM-3, GITR, NKG2A.

For instance: Relativity-123 (NCT05328908), NCT05352672 etc.  

  • RNA-Based Therapies: miRNA (miRNA mimic, anti-miRNA/antagomir) and small interfering RNA (siRNA) can inhibit the expression of any cancer-related genes/mRNAs with high specificity through RNA interference (RNAi), thus representing a remarkable therapeutic tool for targeted therapies and precision medicine. siRNA and miRNA-based therapies have entered clinical trials and recently three novel siRNA-based therapeutics were approved by the Food and Drug Administration (FDA), indicating the beginning of a new era of targeted therapeutics.  Due to the fact that mRNA technology allows the production of diverse vaccines and treatments in a shorter time frame and with reduced expense compared to conventional approaches, there has been a surge in the use of mRNA-based therapeutics in recent years. With the aim of encoding tumour antigens for cancer vaccines, cytokines for immunotherapy, tumour suppressors to inhibit tumour development, chimeric antigen receptors for engineered T cell therapy or genomeediting proteins for gene therapy, many of these therapeutics have shown promising efficacy in preclinical studies, and some have even entered clinical trials. Given the evidence supporting the effectiveness and safety of clinically approved mRNA vaccines, coupled with growing interest in mRNA-based therapeutics, mRNA technology is poised to become one of the major pillars in cancer drug development
  • Microbiome-Modulating Therapies: The gut microbiome is now well acknowledged for its critical role in immunotherapy, with better understanding on host-microbes interaction in the context of cancer treatment. Also, an increasing number of trials have been conducted to evaluate the potential and feasibility of microbiome-targeting approaches to enhance efficacy of cancer treatment in patients. Multiple clinical trials are ongoing (e.g., NCT04924374, NCT05286294, NCT05251389), which aim to provide further evidence regarding the impact of fecal microbiota transplantation in immunotherapy response as well as the associated immune and transcriptomic changes in the gut and tumor tissues.
  • Artificial Intelligence (AI) in IO: Currently AI allows the identification of novel biomarkers that predict response to IO therapies, enabling better patient selection. AI aids in designing highly specific therapies, such as neoantigen vaccines or optimized CAR-T constructs. In conclusion AI helps to accelerates drug development and enhances precision medicine approaches, reducing treatment failures.

#LBS: Having attended the inaugural edition of the London Biotechnology Show 2024, how significant do you believe this event is in broadening the reach and influence of revolutionary breakthroughs within the biotech sector?

 Dr Alexander: The inaugural edition of the London Biotechnology Show 2024 proved to be a pivotal event in expanding the reach and influence of revolutionary breakthroughs within the biotech sector. The meticulous planning and seamless organization ensured a well-curated agenda that catered to the diverse interests of attendees, from seasoned experts to emerging innovators. The event brought together cutting-edge presentations that highlighted groundbreaking advancements, research findings, and transformative solutions. Esteemed thought leaders and industry pioneers shared their expertise, fostering a deeper understanding of how these breakthroughs can shape the future of biotechnology. The highquality content not only educated participants but also sparked meaningful discussions that have the potential to drive innovation beyond the event itself.

Equally significant was the collaborative and interactive environment that the show cultivated. By gathering a diverse mix of participants—ranging from established researchers and industry giants to startups and academics—the event became a hub for exchanging ideas and forging partnerships. Structured networking sessions, panel discussions, and informal meetups offered invaluable opportunities to build connections across disciplines, paving the way for collaborations that can amplify the global impact of biotechnology. This dynamic ecosystem of expertise and innovation underscored the event’s role as a catalyst for translating revolutionary breakthroughs into real-world applications, ultimately broadening their reach and influence within the industry and beyond.